Carbonyl-protecting groups, acetals

Ethylene glycol, HOCH2CH2OH Reacts with ketones or aldehydes in the presence of an acid catalyst to yield acetals that serve as useful carbonyl protecting groups (Section 19.10). 

The next carbonyl protecting group stems from an attempt to retain the carba-nion-stabilising properties of the dithiane 45-acetal whilst increasing its hydro-... 

The carbonyl protecting group in 22 is known as a dioxolane, a cyclic acetal. These acetals are more stable towards hydrolysis than acyclic ones, and therefore require treatment with pyridinium / -toluene-sulfonate (PPTS) under reflux. In general, acetals can only be cleaved using acidic conditions and are stable under basic conditions. 

Via 0,0-Acetals Acyclic and cyclic acetals are the most important carbonyl protecting groups of aldehydes and ketones, and also serve as efficient chiral auxiliaries for the synthesis of enantiomerically pure compounds. ... 

The overall equilibrium constant for formation of the dimethyl acetal of acetaldehyde is 1.58 The comparable value for the addition of water is about Because the position of the equilibrium does not strongly favor product, the synthesis of acetals is carried out in such a way as to drive the reaction to completion. One approach is to use a dehydrating reagent or azeotropic distillation so that the water that is formed is irreversibly removed from the system. Because of the unfavorable equilibrium constant and the relative facility of the hydrolysis, acetals are rapidly converted back to aldehydes and ketones in acidic aqueous solution. The facile hydrolysis makes acetals useful carbonyl protecting groups (see Part B, Section 3.5.3). 

The use of acetals as carbonyl-protecting groups is illustrated by the synthesis of 5-hydroxy-5-phenylpentanal from benzaldehyde and 4-bromobutanal ... 

Addition of Alcohols to Form Acetals (Section 16.7B) Formation of acetals is catalyzed by acid. Acetals are stable to water and aqueous base but are hydrolyzed in aqueous acid. Acetals are valuable as carbonyl-protecting groups. The mechanism for conversion of a hemiacetal to an acetal involves protonation of the OH group of the hemiacetal... 

The Lewis acid-catalyzed Fries rearrangement is performed under strong acidic conditions and therefore reqnires protection of sensitive functional groups. Conversely, the PFR can be achieved nnder milder conditions (organic solvents, nentral media, room temperature, etc.) and is therefore free from this type of problems. Moreover, polyacylation of aromatics is usually difficult to achieve. In the PFR, this problem can be solved by using acetals [144—146] or enol esters [147] as carbonyl protecting groups. Addition of anhydrous K CO is convenient to avoid deprotection [148]. 

Selective reduction of a benzene ring (W. Grimme, 1970) or a C C double bond (J.E. Cole, 1962) in the presence of protected carbonyl groups (acetals or enol ethers) has been achieved by Birch reduction. Selective reduction of the C—C double bond of an a,ft-unsaturated ketone in the presence of a benzene ring is also possible in aprotic solution, because the benzene ring is redueed only very slowly in the absence of a proton donor (D. Caine, 1976). 

X0 to hydroxy compounds. Lower temperatures favor ketone formation and sterically hindered carbonyls, such as 2-thienyl t-butyl ketone, are not reduced. The sensitivity of desulfurization to steric factors is evident by the failure to desulfurize 2,5-di-i-butyl-3-acetylthiophene. The carbonyl groups of both aldehydes and ketones can be protected by acetal formation, as particularly cyclic acetals are stable during desulfurization in methanol at room temperature. " The free aldehydes give primary alcohols on desulfurization. Another method to obtain only keto compounds is to oxidize the mixtures of ketone and secondary alcohol with CrOs after the desulfurization. - Through the desulfurization of 5,5 -diacetyl-2,2, 5, 2"-terthienyl (228), 2,15-hexadecandione (229) has been obtained, which... 

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